Although high-dose chemoradiotherapy with autologous stem cell transplantation has shown some promise in the management of pts. with multiple myeloma, relapse of the underlying disease remains the primary cause of treatment failure. This is a pilot study to explore the possibility that active-specific immunotherapy may be effective in eliminating minimal residual disease remaining after high-dose therapy. Experimental studies in pts. with lymphoma, as well as a single pt. with myeloma have demonstrated the feasibility of immunoglobulin idiotype as a tumor-specific antigen for development of therapeutic vaccines against B-cell malignancies. Pts. will be immunized with myeloma idiotype protein, made immunogenic by conjugation to a carrier (KLH) and administration with GM-CSF as an immunological adjuvant, at several timepoints before and after high-dose therapy. The objective of this study is to test whether cellular and humoral immunity can be induced against the unique idiotype expressed on the patients myeloma pre- and post-transplantation. Pts. will receive a series of 3 vaccinations with myeloma Id-KLH (0.5 mg) administered s.c. together with GM-CSF (250 |g/mg2) for 4 consecutive days 2,3,and 6 months after high-dose therapy with either melphalan/TBI or melphalan/cytoxan followed by autologous peripheral mononuclear stem cell transplantation. 18 pts. have been treated on this study. All pts. have demonstrated responses to KLH, suggesting that immune suppression pro- duced by the BMT conditioning regimen is not an obstacle to active immunization post-BMT. Further- more, 50% of the pts. have demonstrated T-cell responses to idiotype, as demonstrated by autolo- gous idiotype- specific production of cytokines and/or idiotype-specific skin test reactivity in vivo. - Human Subjects